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Agnes Forgacs

Agnes ForgacsCooperating Doctoral Program: Biochemistry and Molecular Biology

EITS Track: Biomedical Toxicology

Education: B.S., University of Guelph

Research Interests:
Sex steroid biosynthesis (steroidogenesis) is essential for proper development and reproductive function. The majority of steroidogenesis in males namely testosterone biosynthesis occurs in the gonads, more specifically in Leydig cells. Endocrine disrupting compound (EDC) exposure can alter steroidogenesis adversely affecting reproductive development and fertility, and is implicated in testicular dysgenesis syndrome, which includes cryptorchidism, hypospadias and testicular cancer. The mechanism by which many EDCs elicit reproductive tract abnormalities is unknown, and the ability to screen chemicals that affect steroidogenesis is lacking.

My dissertation project is to evaluate BLTK1 murine Leydig cells as a novel model for steroidogenesis. Unlike other Leydig cell lines that produce negligible levels of testosterone, BLTK1 cells express all the enzymes required for steroidogenesis and produce testosterone in culture making BLTK1 cells an ideal model for evaluating the effects of EDCs on steroidogenesis. Preliminary studies included the characterization of the cell line to confirm steroidogenic capacity, followed by treatment with known anti-androgenic EDCs to demonstrate that responses observed in BLTK1 cells are comparable to what has been documented in vivo. Finally, triazine herbicides and their chlorometabolites will be evaluated in the BLTK1 Leydig cell model to evaluate parent vs. metabolite effects on testosterone levels as well as to evaluate the mode of action by which these herbicides alter steroidogenesis.

I am also involved in characterizing the hepatic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These studies have involved evaluating the expression of genes involved in mitochondrial oxidative phosphorylation, and whole-genome microarray gene expression and metabolomic profiling of mouse and rat liver tissue. Current work for this project involves the evaluation of human, mouse and rat primary hepatocyte whole-genome gene expression across dose and time to identify species-specific and species-conserved responses elicited by TCDD.

Major Professor: Timothy Zacharewski, Biochemistry and Molecular Biology